Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of Pavlovian-conditioned alcohol-seeking

Authors

  • N. Chaudhri,

    Corresponding author
    • Center for Studies in Behavioural Neurobiology/Groupe de recherche en neurobiologie comportementale, Department of Psychology, Concordia University, Montreal, QC, Canada
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  • C. A. Woods,

    1. Center for Neural Science, New York University, New York, NY, USA
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  • L. L. Sahuque,

    1. Ernest Gallo Clinic & Research Center, University of California at San Francisco, Emeryville, CA, USA
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  • T. M. Gill,

    1. Ernest Gallo Clinic & Research Center, University of California at San Francisco, Emeryville, CA, USA
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  • P. H. Janak

    1. Ernest Gallo Clinic & Research Center, University of California at San Francisco, Emeryville, CA, USA
    2. Department of Neurology, University of California, San Francisco, CA, USA
    3. Wheeler Center for the Neurobiology of Addiction, University of California at San Francisco, San Francisco, CA, USA
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Correspondence: Dr N. Chaudhri, as above.

E-mail: nadia.chaudhri@concordia.ca

Abstract

Environmental contexts associated with drug use promote craving in humans and drug-seeking in animals. We hypothesized that the basolateral amygdala (BLA) itself as well as serial connectivity between the BLA and nucleus accumbens core (NAC core) were required for context-induced renewal of Pavlovian-conditioned alcohol-seeking. Male Long-Evans rats were trained to discriminate between two conditioned stimuli (CS): a CS+ that was paired with ethanol (EtOH, 20%, v/v) delivery into a fluid port (0.2 mL/CS+, 3.2 mL per session) and a CS− that was not. Entries into the port during each CS were measured. Next, rats received extinction in a different context where both cues were presented without EtOH. At test, responding to the CS+ and CS− without EtOH was evaluated in the prior training context. Control subjects showed a selective increase in CS+ responding relative to extinction, indicative of renewal. This effect was blocked by pre-test, bilateral inactivation of the BLA using a solution of GABA receptor agonists (0.1 mm muscimol and 1.0 mm baclofen; M/B; 0.3 μL per side). Renewal was also attenuated following unilateral injections of M/B into the BLA, combined with either M/B, the dopamine D1 receptor antagonist SCH 23390 (0.6 μg per side) or saline infusion in the contralateral NAC core. Hence, unilateral BLA inactivation was sufficient to disrupt renewal, highlighting a critical role for functional activity in the BLA in enabling the reinstatement of alcohol-seeking driven by an alcohol context.

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